Skin is probably the organ most subject to injury. The breach of epithelium triggers tissue mast cells, recruits leukocytes from the blood and stimulates the production of cytokines that activate them. Host survival requires that leukocytes sterilize the wound and that epithelium closes it. However, the antimicrobial molecules released by leukocytes—oxidants, proteases and antimicrobial peptides—can be inimical to epithelial cell survival and proliferation. Control mechanisms must exist that coordinate the phasing of otherwise incompatible actions by diverse host cells in a wound (Martin, 1997; Singer and Clark, 1999).
However, skin repair is a complex process. The process of skin repair can be divided into four phases usually described as inflammation, granulation tissue formation, epithelialization and remodeling of the connective tissue matrix. Each of these phases is complex in itself, and it is clear that for good wound healing, the processes must occur successively and in coordination. Good wound healing can be defined as restoration of the skin, including the dermal and epidermal part, in such a way that the resulting scar tissue maximally resembles the unwounded skin structurally, histologically, functionally, and esthetically obviously, such scar tissue is different from a hypertrophic scar or keloid.
The skin is composed of several sections including the epidermis and dermis, which can be divided into different layers. The upper section is the epidermis, which contains mostly keratinocyte or epithelial cells, some melanocytes and Langerhans cells, and several Merkel cells. Five different layers are found in the epidermis, reflecting the state of keratinization. Proliferating keratinocytes are located at the base of the epidermis, within the stratum basal, and are attached to the dermis via the basement membrane. The dermis is composed of connective tissue, including fibroblasts and other connective tissue cells, and connective tissue matrix substances. Blood vessels, nerves, sensory organs, sweat glands, sebaceous glands, and hair follicles are present in the dermis.
Increased leukocyte elastase activity in mice lacking secretory leukocyte protease inhibitor (SLPI) leads to impaired wound healing due to enhanced activity of TGFb and perhaps other factors. Workers have some data indicating that proepithelin (PEPI) appears to be an epithelial growth factor that can be converted to epithelins (EPIs) in vivo. However, mechanism(s) of this conversion and the consequences thereof are unknown.
Given the complexity of wound healing, further information is needed on the processes by which such healing occurs. Moreover, new therapies for wound healing, particularly of chronic wounds, are needed.